U.S. patent number 8,075,911 [Application Number 11/841,789] was granted by the patent office on 2011-12-13 for transparent transdermal nicotine delivery devices.
This patent grant is currently assigned to Alza Corporation. Invention is credited to Robert M. Gale.
United States Patent |
8,075,911 |
Gale |
December 13, 2011 |
Transparent transdermal nicotine delivery devices
Abstract
A transparent transdermal delivery device for delivering
nicotine which has an Opacity Index of less than 48.6%.
Inventors: |
Gale; Robert M. (Los Altos,
CA) |
Assignee: |
Alza Corporation (Mt. View,
CA)
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Family
ID: |
27381223 |
Appl.
No.: |
11/841,789 |
Filed: |
August 20, 2007 |
Prior Publication Data
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Document
Identifier |
Publication Date |
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US 20080031933 A1 |
Feb 7, 2008 |
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Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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10871458 |
Jun 18, 2004 |
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09464305 |
Dec 15, 1999 |
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60112730 |
Dec 18, 1998 |
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60124679 |
Mar 16, 1999 |
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60126798 |
Mar 30, 1999 |
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Current U.S.
Class: |
424/449; 424/443;
424/448 |
Current CPC
Class: |
A61K
31/4465 (20130101); A61P 25/34 (20180101); A61K
31/465 (20130101); A61K 47/34 (20130101); A61K
47/32 (20130101); A61K 9/0014 (20130101); A61K
9/7084 (20130101); A61K 9/703 (20130101); A61K
9/7023 (20130101); A61K 2800/262 (20130101) |
Current International
Class: |
A61F
13/00 (20060101); A61F 13/02 (20060101) |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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2250025 |
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0 563 507 |
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5632414 |
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Aug 1979 |
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JP |
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60069014 |
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Apr 1985 |
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JP |
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07-165563 |
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Jun 1995 |
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JP |
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07165563 |
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Jun 1995 |
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JP |
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9323925 |
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Jun 1996 |
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JP |
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10279472 |
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Oct 1998 |
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JP |
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WO 91/09592 |
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Jul 1991 |
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WO |
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WO 91/09731 |
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Jul 1991 |
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WO |
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WO 95/24172 |
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Sep 1995 |
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WO |
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WO 97/33581 |
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Sep 1997 |
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WO |
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WO 00/37058 |
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Jun 2000 |
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WO |
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Primary Examiner: Krass; Frederick
Assistant Examiner: Gulledge; Brian
Attorney, Agent or Firm: Stoel Rives LLP Webb; Samuel E.
Colton; Yury M.
Parent Case Text
CLAIM OF PRIORITY
This application is a divisional application of U.S. Ser. No.
10/871,458, filed Jun. 18, 2004, which is a continuation
application of Ser. No. 09/464,305, filed Dec. 15, 1999, now
abandoned which claims the benefit of U.S. provisional patent
applications Ser. No. 60/112,730, filed Dec. 18, 1998; 60/124,679,
filed Mar. 16, 1999; and 60/126,798, filed Mar. 30, 1999, all of
which are incorporated herein by reference.
Claims
I claim:
1. A device for transdermal administration of nicotine, comprising:
a polymeric backing layer comprising a material selected from the
group consisting of PET/EVA laminates, HDPE/EAA/nylon/EAA
multilaminate and a film comprising a graft copolymer formed from
73-77% acrylonitrile and from 23-27% methyl acrylate copolymerized
in the presence of 8-10 parts by weight of butadiene/acrylonitrile
copolymers containing 70% by weight of polymer units derived from
butadiene, a drug reservoir layer containing nicotine carried by
the backing layer, and an adhesive for maintaining the device on
the skin, wherein the device provides delivery of nicotine for a
period of 18-24 hours and, as applied to the skin, exhibits an
Opacity Index of less than 48.6% to permit the skin to which the
device is applied to be visible through the device.
2. The device of claim 1 wherein the backing layer has a nicotine
permeability of less than 1.0 .mu.g/cm.sup.2hr.
3. The device of claim 1, further wherein the Opacity Index of the
device is less than 35.11%.
4. The device of claim 3, wherein the Opacity Index of the device
is less than 20%.
5. The device of claim 1 wherein the backing comprises a PET/EVA
laminate.
6. A device for transdermal nicotine administration, comprising: a
laminate including a polymeric backing layer comprising a material
selected from the group consisting of PET/EVA laminates,
HDPE/EAA/nylon/EAA multilaminate and a film comprising a graft
copolymer formed from 73-77% acrylonitrile and from 23-27% methyl
acrylate copolymerized in the presence of 8-10 parts by weight of
butadiene/acrylonitrile copolymers containing 70% by weight of
polymer units derived from butadiene, a nicotine reservoir layer
having nicotine carried by the backing layer, a rate control
membrane near the nicotine reservoir to face the skin for
controlling nicotine delivery to the skin, and adhesive for
maintaining the device on the skin, wherein the device provides
delivery of nicotine for a period of 18-24 hours and, as applied to
the skin, exhibits an Opacity Index of less than 48.6% to permit
the skin to which the device is applied to be visible through the
device.
Description
FIELD OF THE INVENTION
The present invention relates to transdermal delivery devices for
administering nicotine for use in smoking cessation treatments. In
particular, the invention is directed to transdermal nicotine
delivery devices which are transparent.
BACKGROUND OF THE INVENTION
The transdermal route of parenteral drug delivery provides many
advantages over other administration routes. Transdermal systems
for delivering a wide variety of drugs or other beneficial agents
are described in U.S. Pat. Nos. 3,598,122; 3,598,123; 3,731,683;
3,797,494; 4,031,894; 4,144,317; 4,201,211; 4,286,592; 4,314,557;
4,379,454; 4,435,180; 4,559,222; 4,568,343; 4,573,995; 4,588,580;
4,645,502; 4,698,062; 4,704,282; 4,725,272; 4,781,924; 4,788,062;
4,816,258; 4,849,226; 4,904,475; 4,908,027; 4,917,895; 4,938,759;
4,943,435; 5,004,610; 5,071,656; 5,122,382; 5,141,750; 5,284,660;
5,314,694; 5,342,623; 5,411,740; and 5,635,203, which are hereby
incorporated in their entirety by reference.
The administration of nicotine buccally, nasally and transdermally
to assist a patient desiring to quit smoking has been shown to be
clinically effective in reducing the rate of recidivism. Nicotine
chewing gum and transdermal nicotine are two of the most widely
used forms of nicotine replacement therapy currently available.
Transdermal devices for administering nicotine are disclosed in
U.S. Pat. Nos. 4,597,961; 4,758,434; 4,764,382; 4,839,174;
4,908,213; 4,915,950; 4,943,435; 4,946,853; 5,004,610; 5,016,652;
5,077,104; 5,230,896; 5,411,739; 5,462,745; 5,508,038; 5,599,554;
5,603,947 and 5,726,190, for example, which are hereby incorporated
in their entirety by reference.
Most of the transdermal drug delivery devices of the prior art
utilize an impermeable backing on the skin distal surface of the
device to protect the device from damage and to prevent loss of the
active ingredient(s). In order to improve user satisfaction, these
backing layers are often tinted to a color similar to skin tones.
However, as can be readily appreciated, it is not commercially
practical to provide pigmented backing layers for transdermal
systems which approximate all skin colors.
Another approach that has been taken is to provide transparent
transdermal systems in which all elements forming a device are
sufficiently transparent to permit the natural skin color to be
visible through the device. Marketed products which take this
approach include the ALORA.RTM. and CLIMARA.RTM. estrogen
replacement patches and the DURAGESIC.RTM. transdermal fentanyl
delivery system. When these devices are applied to the skin, the
patient's natural skin color is visible through the patch, making
the presence of the patch extremely inconspicuous. Government
regulations require that these products bear identifying indicia,
but the indicia can be printed on these devices in light colored or
white ink which is not noticeable from a distance of several feet,
but is still readable on close inspection.
Such transparent patches have been found useful with non-volatile
drugs such as fentanyl and hormone replacement steroids, but no
such transparent product has been developed for the delivery of
nicotine.
Nicotine is a liquid alkaloid that is colorless, volatile, strongly
alkaline, readily oxidized, subject to degradation on exposure to
light and highly permeable through not only the human skin, but
also many of the polymers conventionally used in the fabrication of
backing layers and packaging materials for transdermal products
(see for example U.S. Pat. No. 5,077,104). As a result, the backing
layers of the transdermal nicotine delivery devices currently
available utilize opaque, skin-colored multilaminate films which
typically contain a metallized layer, such as aluminum.
Not only do the commercially available transdermal nicotine patches
use opaque backings, but many of these devices, due to the
complexities of handling and processing nicotine, have other
components which are not transparent. For example, the original
Prostep.RTM. transdermal nicotine product used a drug reservoir in
the form of an opaque white gel, held in place by an opaque
adhesive overlay. The HABITROL.RTM. and NICOTROL.RTM. nicotine
patches incorporated absorbant pads in the drug reservoir in which
the nicotine was absorbed.
It has also been proposed to co-administer nicotine with other
substances that improve nicotine cessation therapy. See, for
example, U.S. Pat. Nos. 4,908,213; 5,599,554; and 5,726,190 noted
above, and WO 97/33581.
SUMMARY OF THE INVENTION
The present invention relates to transparent transdermal delivery
devices for the transdermal administration of nicotine, either
alone or in combination with other agents.
Such devices should be sufficiently transparent so that the
subject's skin can be clearly visible through the device when it is
placed on the skin. Identifying indicia can be printed on the
device in light colored or white ink in a manner which is not
noticeable from a short distance, but is readable on close
inspection.
DETAILED DESCRIPTION OF THE INVENTION
Preferred devices of this invention utilize, as the backing layer,
a transparent polymeric film which has a permeability to nicotine
of less than 1 .mu.g/cm.sup.2.hr, preferably less than 0.5
.mu.g/cm.sup.2 hr, a solubility for nicotine that is less than 1%
by weight and preferably less than 0.1%. Such films are preferably
less than about 6 mils thick and most preferably about 2-4 mils
thick. Such films are used in combination with one or more of the
conventional elements of a transdermal device (other than the
removable release liner) such as the drug reservoir, adhesive and
rate controlling membranes, which must also be sufficiently
transparent as to permit the natural skin color to be clearly
visible through the assembled device after placement on the skin.
The finished product should have an Opacity Index of less than
about 48.6%, preferably less than about 35.11% and more preferably
less than 20%.
In addition to being transparent and being sufficiently impermeable
to nicotine, the backing layer must also have sufficient mechanical
strength and physical integrity to maintain the system intact
throughout its intended administration period, which is typically
18-24 hours, and must provide a stable interface with adjoining
layers such as the drug reservoir or adhesive layers of the
transdermal device. This combination of properties is not always
found in one material, and thus the transparent backing layers used
on the devices of this invention can be multilaminate films. In
addition to having a low permeability to nicotine, a backing layer
must also have a low solubility for nicotine. This is because
nicotine is toxic and it could be dangerous for a child, for
example, to lick the backing layer if it contained a substantial
amount of dissolved nicotine.
Suitable polymer materials possessing properties required by this
invention include SCOTCHPAK.RTM. 1220 film, which is a polyethylene
terephthalate/ethylene vinyl acetate (PET EVA), bilaminate film
sold by the 3M Company, Minneapolis, Minn., and SARANEX.RTM. 2057
film, which is a high density polyethylene (HDPE)/ethylene acrylic
acid (EAA)/nylon/EAA multilaminate available from the Dow Chemical
Company, Midland, Mich. Nitrile rubber graft copolymers with
acrylonitrile and methyl acrylate sold as Barex.RTM. films
described in U.S. Pat. No. 5,077,104 noted above, can also be
used.
These films, comprising a graft copolymer formed from about 73-77%
acrylonitrile and from about 23-27% methyl acrylate copolymerized
in the presence of about 8-10 parts by weight of
butadiene/acrylonitrile copolymers containing approximately 70% by
weight of polymer units derived from butadiene are preferred
backing materials.
The transparent transdermal delivery devices of this invention can
be of any of the forms described in the aforementioned patents. The
preferred form, however, comprises a laminate of the backing layer,
a nicotine reservoir layer which contains nicotine dissolved in a
carrier at a concentration below the saturation concentration of
nicotine in the carrier. If the drug reservoir component is self
adhesive, a simple monolithic device could be employed. However, in
many cases it is desirable to include additional components such as
rate controlling membranes, and a separate adhesive layer for
maintaining the devices on the skin such as is described in U.S.
Pat. Nos. 5,004,610 and 5,342,623 listed above. It is further
contemplated that in addition to nicotine, the device may also
contain other drugs or other active substances which cooperate with
or enhance the effect of nicotine in smoking cessation, smoking
replacement or smoking substitution therapy. For all these devices,
a removable release liner would normally be applied on the adhesive
surface of the patch that is used to keep the device on the skin,
which release liner is removed prior to use.
Various materials suited for fabrication of the various components
are known in the art and are disclosed in the aforementioned
patents.
The adhesive component is preferably a pressure sensitive adhesive
including, but not limited to, polysiloxanes, polyacrylates,
polyurethanes, acrylic adhesives including cross linked or uncross
linked acrylic copolymers, vinyl acetate adhesives, ethylene
vinylacetate copolymers, and natural or synthetic rubbers including
polybutadienes, polyisoprenes, and polyisobutylene adhesives, and
mixtures and graft copolymers thereof The devices may also be
provided with hydrophilic water absorbing polymers known in the art
such as polyvinyl alcohol and polyvinyl pyrolidone individually or
in combination. The adhesive can be used to form a monolithic
delivery device in which the nicotine is dissolved in the adhesive
to form a self-adhesive drug reservoir. Alternatively, the adhesive
can be applied to the surface of a non-adhesive reservoir in which
nicotine is dissolved, to form a multilaminate device. A
rate-controlled membrane can also be interfaced between the
nicotine reservoir and the adhesive, as is known to the art.
The nicotine can be administered in combination with another agent
which could include anti-anxiolytics, antihypertensives,
antidepressants, and appetite suppressants, such as fluoxetine,
caffeine, buspirone, phenylpropanolamine, clonidine, paroxetine,
citalopram, and sertraline.
The nicotine in the device is present in the reservoir at a
subsaturated condition (i.e. less than unit activity) such that no
undissolved nicotine is present in the reservoir. If other agents
are present in the device, they are preferably present fully
dissolved, but can be present in undissolved form so long as the
end product displays the proper degree of transparency.
In the present invention, nicotine and optionally other agents to
be co-administered are delivered through the skin or other body
surface at a therapeutically effective rate for a predetermined
time period which for nicotine is preferably 16-24 hours.
The transdermal therapeutic devices of the present invention are
prepared in a manner known in the art, such as by those procedures
described in the transdermal device patents listed previously
herein.
The following example is offered to illustrate the practice of the
present invention and is not intended to limit the invention in any
manner.
EXAMPLE 1
Various commercially available transdermal patches were tested to
determine their transparency and compared to the transparent
nicotine patches according to this invention. The nicotine patches
were prepared as set forth in Example IV of U.S. Pat. No. 5,004,610
with a PET/EVA (SCOTCHPAK.RTM. 1220 film, 3M, Minneapolis, Minn.)
or SARANEX.RTM. film (Dow Chemical Company, Midland, Mich.) backing
substituted for the SCOTCHPAK 1006 film backing. The light
transmitted through the various systems was measured by a MACBETH
1500/Plus color measurement system (Kollmorgem Instruments Corp.,
Newburgh, N.Y.). Table 1 shows the Opacity Index, which is the
percentage of incidental light which is absorbed by passage through
the device, for the various systems tested.
TABLE-US-00001 TABLE 1 Patch Opacity Patch Opacity Index MINITRAN
.RTM. 48.6% ALORA .RTM. 20.21% FEMPATCH .RTM. 35.11% CLIMARA .RTM.
19.33% Ex. 1 - Nicotine with SARANEX .RTM. backing 17.04% Ex. 1 -
Nicotine with PET/EVA backing 19.66%
The MINITRAN.RTM. nitroglycerine system is clearly visible from a
distance of about 5 feet, whereas the FEMPATCH.RTM. patch is
significantly less noticeable. The ALORA.RTM., CLIMARA.RTM. and
NICODERM.RTM. patches, however, are extremely inconspicuous.
Accordingly, transdermal devices according to this invention should
have an Opacity Index less than 48.6%, preferably less than 35.11%,
more preferably less than 20%.
Having thus generally described our invention and preferred
embodiments thereof, it is apparent that various modifications and
substitutions will be apparent to workers skilled in the art. These
modifications and substitutions can be made without departing from
the scope of our invention which is limited only by the following
claims.
* * * * *
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